Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2

Abstract We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-...

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Autores principales:	Ikhyun Jun, Yong Woo Ji, Seung-il Choi, Bo Ram Lee, Ji Sang Min, Eung Kweon Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b718696abfc43ab9552600f5aead0be
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spelling	oai:doaj.org-article:8b718696abfc43ab9552600f5aead0be2021-12-02T14:02:54ZCompound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 210.1038/s41598-021-86414-92045-2322https://doaj.org/article/8b718696abfc43ab9552600f5aead0be2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86414-9https://doaj.org/toc/2045-2322Abstract We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-corrected visual acuity test, intraocular pressure measurement, slit-lamp examination, and slit-lamp photograph analysis) and direct Sanger sequencing of whole-TGFBI. The patient’s family was tested to determine the pedigrees. Five novel mutations (p.(His174Asp), p.(Ile247Asn), p.(Tyr88Cys), p.(Arg257Pro), and p.(Tyr468)) and two known mutations (p.(Asn544Ser) and p.(Arg179)) in TGFBI were identified, along with p.(Arg124His), in the patients. Trans-phase of TGFBI second mutations was confirmed by pedigree analysis. Multiple, extensive discoid granular, and increased linear deposits were observed in the probands carrying p.(Arg124His) and other nonsense mutations. Some patients who had undergone phototherapeutic keratectomy experienced rapid recurrence (p.(Ile247Asn) and p.(Asn544Ser)); however, the cornea was well-maintained in a patient who underwent deep anterior lamellar keratoplasty (p.(Ile247Asn)). Thus, compound heterozygosity of TGFBI is associated with the phenotypic variability of TGFBI corneal dystrophies, suggesting that identifying TGFBI second mutations may be vital in patients with extraordinarily severe phenotypes. Our findings indicate the necessity for a more precise observation of genotype–phenotype correlation and additional care when treating TGFBI corneal dystrophies.Ikhyun JunYong Woo JiSeung-il ChoiBo Ram LeeJi Sang MinEung Kweon KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ikhyun Jun Yong Woo Ji Seung-il Choi Bo Ram Lee Ji Sang Min Eung Kweon Kim Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
description	Abstract We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-corrected visual acuity test, intraocular pressure measurement, slit-lamp examination, and slit-lamp photograph analysis) and direct Sanger sequencing of whole-TGFBI. The patient’s family was tested to determine the pedigrees. Five novel mutations (p.(His174Asp), p.(Ile247Asn), p.(Tyr88Cys), p.(Arg257Pro), and p.(Tyr468)) and two known mutations (p.(Asn544Ser) and p.(Arg179)) in TGFBI were identified, along with p.(Arg124His), in the patients. Trans-phase of TGFBI second mutations was confirmed by pedigree analysis. Multiple, extensive discoid granular, and increased linear deposits were observed in the probands carrying p.(Arg124His) and other nonsense mutations. Some patients who had undergone phototherapeutic keratectomy experienced rapid recurrence (p.(Ile247Asn) and p.(Asn544Ser)); however, the cornea was well-maintained in a patient who underwent deep anterior lamellar keratoplasty (p.(Ile247Asn)). Thus, compound heterozygosity of TGFBI is associated with the phenotypic variability of TGFBI corneal dystrophies, suggesting that identifying TGFBI second mutations may be vital in patients with extraordinarily severe phenotypes. Our findings indicate the necessity for a more precise observation of genotype–phenotype correlation and additional care when treating TGFBI corneal dystrophies.
format	article
author	Ikhyun Jun Yong Woo Ji Seung-il Choi Bo Ram Lee Ji Sang Min Eung Kweon Kim
author_facet	Ikhyun Jun Yong Woo Ji Seung-il Choi Bo Ram Lee Ji Sang Min Eung Kweon Kim
author_sort	Ikhyun Jun
title	Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
title_short	Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
title_full	Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
title_fullStr	Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
title_full_unstemmed	Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2
title_sort	compound heterozygous mutations in tgfbi cause a severe phenotype of granular corneal dystrophy type 2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8b718696abfc43ab9552600f5aead0be
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Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2

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